Conducting ethical review of investigator-initiated trials （IIT） is one of the important links to ensure the quality of research projects. Currently， the quality of ethical review for IIT projects is greatly influenced by the personal factors of committee members， which to some extent affects the ethical review committee’s judgments of research risks and benefits. Based on the previously developed Risk-Benefit Assessment Scale for Clinical Research， this paper established an ethical review decision-making pathway based on risk-benefit assessment， that is， proposed the “four-step method” for ethical review risk-benefit assessment， including evaluating the research benefits， assessing the research risks， constructing a risk-benefit matrix， and establishing an ethical review pathway. The “four-step method” helps to reduce the impact of committee members’ subjective/intuitive judgments on the quality of ethical review， assists in promoting the implementation of multi-center ethical review policy， narrows the gap in the quality of ethical review among different medical institutions， and provides clearer guidance for the risk judgments of scientific research management and ethical review departments.

Objective:To analyze the risk factors of hypocalcemia in 3-5 stages of chronic kidney disease (CKD) patients with hyperkalemia and non-dialysis after potassium lowering therapy.Methods:Clinical data of 3-5 stages of CKD patients with hyperkalemia and non-dialysis treated in Linyi Central Hospital from January 2019 to November 2024 were collected through the electronic medical record system. According to whether the corrected calcium level after potassium lowering treatments was lower than 2.12 mmol/L, the patients were divided into hypocalcemia group and non-hypocalcemia group. The gender, age, body mass index, primary disease, disease duration, comorbidity, use of potassium lowering drugs, concomitant medication, and blood potassium, corrected calcium, carbon dioxide binding capacity, blood magnesium, blood phosphorus, estimated glomerular filtration rate, and total parathyroid hormone before potassium lowering treatments between the 2 groups were compared. Multiple logistic regression analysis was used to identify the risk factors for hypocalcemia in 3-5 stages of CKD patients with hyperkalemia and non-dialysis after potassium lowering therapy.Results:A total of 260 patients were entered, including 58 with blood calcium lower than 2.12 mmol/L, and incidence of hypocalcemia was 22.3%. The differences in the baseline corrected calcium, blood phosphorus, carbon dioxide binding capacity, estimated glomerular filtration rate, and total parathyroid hormone between the hypocalcemia group and the non-hypocalcemia group were statistically significant ( P<0.05). The factors with P<0.1, including primary disease, baseline corrected calcium, blood phosphorus, carbon dioxide binding capacity, estimated glomerular filtration rate, and total parathyroid hormone, were included in the multivariate logistic regression analysis. The results showed that the probability of hypocalcemia at baseline corrected calcium levels of 2.12-2.21, 2.22-2.31, and 2.32-2.41 mmol/L was 49.306 times, 13.651 times, and 13.342 times that of at ≥2.42 mmol/L, respectively. Low carbon dioxide binding capacity (odds ratio=0.909, 95% confidence interval: 0.836-0.987) was also a risk factor of hypocalcemia in 3-5 stages CKD patients with hyperkalemia and non-dialysis after potassium lowering therapy. Conclusions:Three to five stages of CKD patients with hyperkalemia and non-dialysis are prone to hypocalcemia after potassium lowering therapy. The low levels of baseline corrected calcium and carbon dioxide binding may be closely related to the occurrence of hypocalcemia in 3-5 stages of CKD patients with hyperkalemia and non-dialysis after potassium lowering therapy.

Objective:To investigate the effects of roxadustat on thyroid function in patients with renal anemia undergoing peritoneal dialysis.Methods:After applying the inclusion and exclusion criteria, a retrospective analysis was conducted on the clinical data of 151 patients undergoing peritoneal dialysis who were treated with either roxadustat or erythropoietin at Linyi Central Hospital from January 2019 to December 2023. The patients were divided into two groups based on their treatment: roxadustat group ( n = 88) and erythropoietin group ( n = 63). Patient age, sex, body mass index, urine output, duration of illness, primary disease, comorbidities, estimated glomerular filtration rate, total parathyroid hormone levels, and thyroid nodule status were recorded. Thyroid-stimulating hormone (TSH), free triiodothyronine, and free thyroxine levels before and after treatment were compared between the two groups. A decrease in TSH of more than one-third after treatment compared with the pre-treatment level was defined as a significant decrease in TSH. Multivariate logistic regression analysis was conducted to investigate the independent risk factors associated with a significant decrease in TSH in patients with renal anemia undergoing peritoneal dialysis. Results:After treatment, the roxadustat group showed significant decreases in TSH [1.84 (1.06, 2.67) U/L] and FT4 [(11.82 ± 3.56) pmol/L] compared with pre-treatment levels [2.58 (1.67, 3.42) U/L, (14.89 ± 3.27) pmol/L, Z = -3.42, t = -5.97, both P < 0.05]. After treatment, both TSH and FT4 levels were significantly lower in the roxadustat group than those in the erythropoietin group [2.80 (1.61, 3.78) U/L, (15.49 ± 3.24) pmol/L, Z = -3.36, t = 6.49, both P < 0.05]. Multivariate logistic regression analysis indicated that the use of roxadustat was an independent risk factor for a significant decrease in TSH in patients with renal anemia undergoing peritoneal dialysis [ OR = 7.621, 95% CI (3.195, 18.178)]. Conclusions:Roxadustat may lower TSH and FT4 levels in patients with renal anemia undergoing peritoneal dialysis.

Cardiovascular disease(CVD)is the leading cause of death among patients with non-alcoholic fatty liver disease(NAFLD),which is also recognized as an independent risk factor for CVD.Exercise has emerged as a prom-ising therapeutic approach that can ameliorate a range of conditions,including those related to the cardiovascular and en-docrine systems.Recent research has highlighted the critical role of the integrated stress response(ISR)in the mecha-nisms and manifestations of these diseases.Notably,exercise influences ISR protein markers,regulates protein expres-sion,alleviates stress levels,and ultimately impacts disease onset and progression.Current studies suggest that the effects of ISR modulation through various exercise conditions differ for the heart and liver.However,evidence indicates that un-der specific circumstances,exercise can engage the PERK and GCN2 pathways to inhibit the ISR,thereby regulating glu-cose and lipid metabolism,apoptosis,and endoplasmic reticulum stress.These actions contribute to the protection of car-diac and hepatic function,ultimately improving outcomes in CVD and NAFLD.This review aims to provide novel insights and a theoretical foundation for the role of exercise in mitigating the onset of NAFLD,CVD,and related disorders.

Cardiovascular disease(CVD)is the leading cause of death among patients with non-alcoholic fatty liver disease(NAFLD),which is also recognized as an independent risk factor for CVD.Exercise has emerged as a prom-ising therapeutic approach that can ameliorate a range of conditions,including those related to the cardiovascular and en-docrine systems.Recent research has highlighted the critical role of the integrated stress response(ISR)in the mecha-nisms and manifestations of these diseases.Notably,exercise influences ISR protein markers,regulates protein expres-sion,alleviates stress levels,and ultimately impacts disease onset and progression.Current studies suggest that the effects of ISR modulation through various exercise conditions differ for the heart and liver.However,evidence indicates that un-der specific circumstances,exercise can engage the PERK and GCN2 pathways to inhibit the ISR,thereby regulating glu-cose and lipid metabolism,apoptosis,and endoplasmic reticulum stress.These actions contribute to the protection of car-diac and hepatic function,ultimately improving outcomes in CVD and NAFLD.This review aims to provide novel insights and a theoretical foundation for the role of exercise in mitigating the onset of NAFLD,CVD,and related disorders.

Objective:To analyze the risk factors of hypocalcemia in 3-5 stages of chronic kidney disease (CKD) patients with hyperkalemia and non-dialysis after potassium lowering therapy.Methods:Clinical data of 3-5 stages of CKD patients with hyperkalemia and non-dialysis treated in Linyi Central Hospital from January 2019 to November 2024 were collected through the electronic medical record system. According to whether the corrected calcium level after potassium lowering treatments was lower than 2.12 mmol/L, the patients were divided into hypocalcemia group and non-hypocalcemia group. The gender, age, body mass index, primary disease, disease duration, comorbidity, use of potassium lowering drugs, concomitant medication, and blood potassium, corrected calcium, carbon dioxide binding capacity, blood magnesium, blood phosphorus, estimated glomerular filtration rate, and total parathyroid hormone before potassium lowering treatments between the 2 groups were compared. Multiple logistic regression analysis was used to identify the risk factors for hypocalcemia in 3-5 stages of CKD patients with hyperkalemia and non-dialysis after potassium lowering therapy.Results:A total of 260 patients were entered, including 58 with blood calcium lower than 2.12 mmol/L, and incidence of hypocalcemia was 22.3%. The differences in the baseline corrected calcium, blood phosphorus, carbon dioxide binding capacity, estimated glomerular filtration rate, and total parathyroid hormone between the hypocalcemia group and the non-hypocalcemia group were statistically significant ( P<0.05). The factors with P<0.1, including primary disease, baseline corrected calcium, blood phosphorus, carbon dioxide binding capacity, estimated glomerular filtration rate, and total parathyroid hormone, were included in the multivariate logistic regression analysis. The results showed that the probability of hypocalcemia at baseline corrected calcium levels of 2.12-2.21, 2.22-2.31, and 2.32-2.41 mmol/L was 49.306 times, 13.651 times, and 13.342 times that of at ≥2.42 mmol/L, respectively. Low carbon dioxide binding capacity (odds ratio=0.909, 95% confidence interval: 0.836-0.987) was also a risk factor of hypocalcemia in 3-5 stages CKD patients with hyperkalemia and non-dialysis after potassium lowering therapy. Conclusions:Three to five stages of CKD patients with hyperkalemia and non-dialysis are prone to hypocalcemia after potassium lowering therapy. The low levels of baseline corrected calcium and carbon dioxide binding may be closely related to the occurrence of hypocalcemia in 3-5 stages of CKD patients with hyperkalemia and non-dialysis after potassium lowering therapy.

Objective:To investigate the effects of roxadustat on thyroid function in patients with renal anemia undergoing peritoneal dialysis.Methods:After applying the inclusion and exclusion criteria, a retrospective analysis was conducted on the clinical data of 151 patients undergoing peritoneal dialysis who were treated with either roxadustat or erythropoietin at Linyi Central Hospital from January 2019 to December 2023. The patients were divided into two groups based on their treatment: roxadustat group ( n = 88) and erythropoietin group ( n = 63). Patient age, sex, body mass index, urine output, duration of illness, primary disease, comorbidities, estimated glomerular filtration rate, total parathyroid hormone levels, and thyroid nodule status were recorded. Thyroid-stimulating hormone (TSH), free triiodothyronine, and free thyroxine levels before and after treatment were compared between the two groups. A decrease in TSH of more than one-third after treatment compared with the pre-treatment level was defined as a significant decrease in TSH. Multivariate logistic regression analysis was conducted to investigate the independent risk factors associated with a significant decrease in TSH in patients with renal anemia undergoing peritoneal dialysis. Results:After treatment, the roxadustat group showed significant decreases in TSH [1.84 (1.06, 2.67) U/L] and FT4 [(11.82 ± 3.56) pmol/L] compared with pre-treatment levels [2.58 (1.67, 3.42) U/L, (14.89 ± 3.27) pmol/L, Z = -3.42, t = -5.97, both P < 0.05]. After treatment, both TSH and FT4 levels were significantly lower in the roxadustat group than those in the erythropoietin group [2.80 (1.61, 3.78) U/L, (15.49 ± 3.24) pmol/L, Z = -3.36, t = 6.49, both P < 0.05]. Multivariate logistic regression analysis indicated that the use of roxadustat was an independent risk factor for a significant decrease in TSH in patients with renal anemia undergoing peritoneal dialysis [ OR = 7.621, 95% CI (3.195, 18.178)]. Conclusions:Roxadustat may lower TSH and FT4 levels in patients with renal anemia undergoing peritoneal dialysis.

The aim of this study was to investigate the effects of high-intensity interval training(HIIT)on lipopolysaccharide(LPS)-induced septic myocardial injury in mice and the roles of NLRP3 inflammasome and macrophage M1 polarization in the process.C57BL/6 male mice were randomly divided into 4 groups:control(CON)group,LPS(L)group,HIIT+saline injection(E)group,and HIIT+LPS(EL)group.Six weeks of HIIT intervention was followed by intraperitoneal injection of LPS,and cardiac function indexes were measured by echocardiography 12 hours post the injection.Hematoxylin-eosin(HE)staining was used to evaluate the morphology and pathological characteristics of myocardium for assessing myocardial damage score;enzyme-linked immunosorbent assay(ELISA)was used to test the content of myocardial damage indicators(AST,CK-MB,LDH);RT-PCR was used to detect the relative mRNA levels of NLRP3 inflammasome(NLRP3,Caspase-1),atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),myeloperoxidase(MPO)and macrophage M1-associated inflammasome factors(IL-1β,TNF-α,IL-6);Western blot was applied to measure the protein expression of inducible nitric oxide synthase(iNOS)and apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)in cardiac tissues;immunofluorescence staining was used to detect the protein expression of NLRP3 inflammasome,ASC,IL-18 and iNOS.Compared with the CON group,mice in the LPS group showed obvious decrease in body weight,a significant decrease in EF and FS,a significant increase in LVESD and LVEDD,obvious pathological damage in myocardial tissue,a significant increase in myocardial damage fraction,a significant increase in serum myocardial damage indexes,and a significant increase in the expression levels of BNP,MPO,NLRP3 inflammasome,iNOS,IL-1β,IL-6 and TNF-α.HIIT treatment could reverse these changes mentioned above in model mice.In conclusion,6 weeks of HIIT inhibits the activation of LPS-induced NLRP3 inflammasome and suppressed macrophage M1-type polarization,thereby combating septic myocardial injury.

Objective:The aim is to construct an evaluation framework for clinical research benefits,and provide a reference for the formulate of evaluation standards for clinical research benefits.Methods:The Delphi method was used to carry out expert consultation,and the mean,score of importance,coefficient of variation and coordination,etc.of evaluation indicators were summarized and calculated,to screen evaluation indicators for clinical research benefits.Results:Twenty-three experts in this field were selected for correspondence,and their enthusiasm was 100%in both rounds,the authority coefficients were≥0.90,and Kendall's coefficients of concordance were<0.25(P<0.001).By referring to the mean and coefficient of variation of the indicators,as well as combining them with expert suggestions,an evaluation framework for clinical research benefits was ultimately formed with 2 primary indicators,5 secondary indicators,and 8 tertiary indicators.Conclusion:The evaluation framework for clinical research benefits constructed in this paper can comprehensively evaluate the research benefits,as well as provide a basis for reasonably determining the research risk-benefit ratio and developing quantitative evaluation tools for clinical research benefits.

Objective:Currently,the medical Institutional Review Board(IRB)mainly rely on experience to analyse the risks and benefits of clinical research,lacking an assessment framework of risks and benefits.Methods:Using grounded theory,interviews were conducted on 29 ethical review workers in China.Through open coding,spindle coding,and selective coding,the framework of risks and benefits for clinical research in China was constructed.NVivo11 software was used for data storage,organization,encoding,and analysis.Results:A framework of risks and benefits for clinical research was proposed based on China's national conditions.Clinical research risks consisted of physiological risk,psychological risk,economic risk,and social risk.Research benefits consisted of subject benefits and society benefits.Conclusion:This paper systematically explained the connotation of the risks and benefits of clinical research,and constructed a framework of the risks and benefits of clinical research applicable to China.It has certain innovations in theoretical research,and also provides use for reference for researchers and ethics committees to evaluate risks and potential benefits in clinical research.